ArticleStem cell research & therapy2018
Targeted genome engineering in human induced pluripotent stem cells from patients with hemophilia B using the CRISPR-Cas9 system.
Article in Stem cell research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 102 citations in OpenAlex.
- Therapeutic Effects of Adipose-Derived Mesenchymal Stem Cell Exosome like Nanovesicles on Granulosa Cell Function in a Mouse Model of Polycystic Ovarian Syndrome: Involvement of FOXO3, Map1lc3b, SF-1 Genes.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Integrating HTS and CRISPR/Cas for next-generation nucleic and non-nucleic acid diagnostics.Molecular genetics and genomics : MGG · 2026Review
- Article
- Human Genome Safe Harbor Sites: A Comprehensive Review of Criteria, Discovery, Features, and Applications.Cells · 2026Review
- Exploring gene editing as a potential therapeutic strategy for hemophilia.Frontiers in bioengineering and biotechnology · 2026Review
- Advances in endothelial cell targeting by AAV vectors.Acta biochimica Polonica · 2026Review
- Gene Editing of Pluripotent Stem Cell-Derived Hepatic Cells for Liver Disease Modeling and Therapeutic Development.Biomolecules & therapeutics · 2026Review
- Application of Induced Pluripotent Stem Cells (iPSCs) in Hereditary and Viral Diseases of the Liver: Modeling and Treatment.International journal of molecular sciences · 2025Review
- Off-target effects in CRISPR-Cas genome editing for human therapeutics: Progress and challenges.Molecular therapy. Nucleic acids · 2025Review
- Precise measurement of CRISPR genome editing outcomes through single-cell DNA sequencing.Molecular therapy. Methods & clinical development · 2025Article
- Development of iPSC-derived FIX-secreting hepatocyte sheet as a novel treatment tool for hemophilia B treatment.Stem cell research & therapy · 2025Article
- Transformative approaches in hemophilia management: from traditional therapies to prenatal stem cell treatment.Frontiers in bioengineering and biotechnology · 2025Review
- CRISPR/Cas System: A Powerful Strategy to Improve Monogenic Human Diseases as Therapeutic Delivery; Current Applications and Challenges.Current gene therapy · 2025Review
- Innovations in RNA therapy for hemophilia.Blood · 2023Review
- CRISPR/Cas9 Landscape: Current State and Future Perspectives.International journal of molecular sciences · 2023Review
- Recent Advances in CRISPR/Cas9 Delivery Approaches for Therapeutic Gene Editing of Stem Cells.Stem cell reviews and reports · 2023Review
- Propensity of Patient-Derived iPSCs for Retinal Differentiation: Implications for Autologous Cell Replacement.Stem cells translational medicine · 2023Article
- CRISPR-Mediated In Situ Introduction or Integration ofInternational journal of molecular sciences · 2023Article
- "iPSC-derived liver organoids and inherited bleeding disorders: Potential and future perspectives".Frontiers in physiology · 2023Review
- Bioengineering liver microtissues for modeling non-alcoholic fatty liver disease.EXCLI journal · 2023Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundReplacement therapy for hemophilia remains a lifelong treatment. Only gene therapy can cure hemophilia at a fundamental level. The clustered regularly interspaced short palindromic repeats-CRISPR associated nuclease 9 (CRISPR-Cas9) system is a versatile and convenient genome editing tool which can be applied to gene therapy for hemophilia.
methodsA patient's induced pluripotent stem cells (iPSCs) were generated from their peripheral blood mononuclear cells (PBMNCs) using episomal vectors. The AAVS1-Cas9-sgRNA plasmid which targets the AAVS1 locus and the AAVS1-EF1α-F9 cDNA-puromycin donor plasmid were constructed, and they were electroporated into the iPSCs. When insertion of F9 cDNA into the AAVS1 locus was confirmed, whole genome sequencing (WGS) was carried out to detect the off-target issue. The iPSCs were then differentiated into hepatocytes, and human factor IX (hFIX) antigen and activity were measured in the culture supernatant. Finally, the hepatocytes were transplanted into non-obese diabetic/severe combined immunodeficiency disease (NOD/SCID) mice through splenic injection.
resultsThe patient's iPSCs were generated from PBMNCs. Human full-length F9 cDNA was inserted into the AAVS1 locus of iPSCs of a hemophilia B patient using the CRISPR-Cas9 system. No off-target mutations were detected by WGS. The hepatocytes differentiated from the inserted iPSCs could secrete hFIX stably and had the ability to be transplanted into the NOD/SCID mice in the short term.
conclusionsPBMNCs are good somatic cell choices for generating iPSCs from hemophilia patients. The iPSC technique is a good tool for genetic therapy for human hereditary diseases. CRISPR-Cas9 is versatile, convenient, and safe to be used in iPSCs with low off-target effects. Our research offers new approaches for clinical gene therapy for hemophilia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.